Previous studies in our laboratory have established that a significant number of patients with active coccidioidomycosis have elevated levels of circulating immune complexes, that immune complexes are of intermediate size sedimenting between 6.6S and 19S markers in sucrose gradient ultracentrifugation, and that immune complexes are comprised of Coccidioides antigen and antibody. Immune complexes, detected by Clq binding assays, have been demonstrated in sera of 40 of 96 (42%) patients with active coccidioidomycosis as compared to only 2 of 21 (10%) of patients with inactive disease (p less than 0.005) and 0 of 17 healthy, coccidioidin skin-test positive subjects (p less than 0.01). Immune complex formation correlated with disease involvement. Nine of 15 (60%) patients with coccidioidomycosis involving two or more organs had elevated immune complexes as compared to 27 of 75 (35%) patients with single organ involvement. The role of immune complexes in the pathogenesis of this disease is not known. Both the size and composition of immune complexes affect their clearance from the circulation. Intermediate size (11S) immune complexes, such as those detected in coccidioidomycosis, may be deposited effect of immune complexes relates to their immunosuppressive properties. Studies in other biological systems have shown the immune complexes can inhibit polymorphonuclear leukocyte chemotaxis, antibody-dependent cell-mediated cytotoxicity, natural killer cell cytotoxicity, T cell dependent delayed-type hypersensitivity, and macrophage Fc receptor function. The objectives of the proposed studies are to: (i) establish a temporal relationship between immune complex formation and disease severity in patients with coccidioidomycosis; (ii) characterize immune complexes in terms of antibody and antigen composition; (iii) assess immunosuppressive effects of immune complexes on host response to C. immitis; and (iv) assess immune complex deposition in host tissues.